PDF herunterladen
Neuropediatrics
DOI: 10.1055/a-2708-3016
Original Article

Exploring Secondary Biotinidase Deficiency and Biotin Supplementation in PMM2-CDG

Authors

  • Nastassja Himmelreich

    1   Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany

  • Sven F. Garbade

    1   Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany

  • Jürgen G. Okun

    1   Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany

  • Simone Hengst

    1   Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany

  • Virginia Geiger

    1   Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany

  • Rita Barone

    2   Child Neuropsychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
    3   Research Unit of Rare Diseases and Neurodevelopmental Disorders, Oasi Research Institute-IRCCS, Troina, Italy

  • Saskia B. Wortmann

    4   University Children's Hospital, Paracelsus Medical University (PMU), Salzburg, Austria
    5   Integriertes Sozialpädiatrisches Zentrum (iSPZ), Munich, Germany

  • Christian Thiel 

    1   Department I, Medical Faculty Heidelberg, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany

Funding Information C.T. and N.H. were supported by the Deutsche Forschungsgemeinschaft (FOR2509: TH1461/7-2) and the European Commission (E-Rare-3 Joint Transnational Call 2018/EUROGLYCAN-omics).Supplementary Material is available at https://doi.org/10.1055/a-2708-3016.
Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints
Preview

Abstract

Background

The congenital disorders of glycosylation (CDG) encompass >190 multiorgan disorders with predominantly neurodevelopmental phenotypes with no causative treatment available. The glycoprotein biotinidase (BTD) provides biotin, an essential cofactor for carboxylases in ubiquitous metabolic pathways. Individuals with (partial) BTD deficiency (BTDD) and CDG patients show overlapping phenotypes like movement disorders, seizures, and neurodevelopmental issues. Biotin is a water-soluble, inexpensive, and safe food supplement. Patients with primary BTDD respond well to oral biotin supplement. We here explore secondary BTDD and the effect of biotin supplementation in PMM2-CDG in an initial open-label study.

Methods

BTD activity in dried blood spots from 29 individuals with PMM2-CDG indicated a mean reduction to 27% (range: 23.0–40.5%) at group level. Patients (mean: 19.6 ± 11.9 years) were supplemented with 10 mg biotin daily for 12 months. The parents/caretaker reported positive responses in 62 to 69% of patients across seven (performance, social, at home, self-control, self-care, leisure, health) of the nine categories covered by the Adaptive Behavior Assessment System-II (ABAS-II) questionnaires. The reported positive effect of biotin supplementation differed between age groups, ranging from 54% (16–43 years) via 62% (2–5 years) to 80% (6–13 years). Its effect was reported to be the highest in the moderate to severely affected patient subgroups, with significant improvements in home functioning, health, performance, leisure, self-control. No adverse effects were reported.

Conclusion

Given the absence of other treatments, the supportive effect of Biotin in PMM2-CDG deserves further exploration.

Keywords

congenital disorders of glycosylation - therapy - vitamin H - biotinidase deficiency - treatment - seizures - movement disorder - rare disease

Data Availability Statement

The data that support the findings of this study are available upon reasonable request.


Supplementary Material



Publikationsverlauf

Eingereicht: 16. Mai 2025

Angenommen: 23. September 2025

Artikel online veröffentlicht:
06. Oktober 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany